A French study suggests HHV-6 is a cause of confluent necrosis, the most common form of pathology found in liver transplant patients. In the study, liver tissue samples from 26 patients with graft hepatitis of unknown origin were investigated for the presence of HHV-6 DNA. HHV-6 was detected in 10 patients (38.5%), with a reported median viral load of 3.84 log10 copies/10(6) cells. Confluent periportal necrosis was observed in 4 of the 10 HHV-6+ patients, and found to be significantly associated with high viral load. All 4 of these patients responded to antiviral therapy. Of note, mild hepatitis was also observed in 4 patients with low intragraft HHV-6 levels, as well as in 2 patients with elevated viral loads (both of these patients were highly immunosuppressed). This finding is consistent with data from a German study of 173 liver transplants published last year that determined high-level intrahepatic HHV-6 DNA detection, and not low-level detection, was a significant risk factor for reduced survival following liver transplantation (Pischke 2012).

Interestingly, a clear distinction was observed among patients in the cohort that went on to develop graft hepatitis in the absence of HHV-6. All cases of HHV-6-negative graft hepatitis disclosed lobular necrotico-inflammatory activity without periportal necrosis. For this reason, the authors conclude that the presence of confluent periportal necrosis suggests HHV-6-induced graft hepatitis.

It should also be pointed out that only 2 of 7 HHV-6+ patients were found to have detectable levels of HHV-6 in the PBMCs. Other investigators have reported similar findings regarding the absence of HHV-6 DNA in the plasma despite significant organ disease. For example, a post-mortem diagnosis found HHV-6 in nearly one-third of tissue samples from patients who died of hepatitis of unknown origin (Katano 2011) despite the absence of detectable DNA in the plasma. Another case report described a patient who died of persistent HHV-6 myocarditis with no trace of HHV-6 DNA in the plasma (Leveque 2011).

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The HHV-6 Foundation in a non-profit entity founded to encourage scientific exchange between investigators and to provide pilot grants for promising scientific and clinical research on the under- appreciated viruses HHV-6A and HHV-6B.

The Foundation sponsors international conferences and supports scientists and clinicians seeking to clarify the role of the two HHV-6 viruses in disease. Since HHV-6A and HHV-6B can smolder in the brain and other organs without circulating in the peripheral blood or plasma, identifying chronic infection is a challenge.